Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study.
Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study.
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DOI：
10.1093/brain/aww160
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发表时间：
2016-09
期刊：
影响因子：
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通讯作者：
Nordberg A
中科院分区：
文献类型：
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作者：
Leuzy A;Chiotis K;Hasselbalch SG;Rinne JO;de Mendonça A;Otto M;Lleó A;Castelo-Branco M;Santana I;Johansson J;Anderl-Straub S;von Arnim CA;Beer A;Blesa R;Fortea J;Herukka SK;Portelius E;Pannee J;Zetterberg H;Blennow K;Nordberg A
β淀粉样蛋白的PET和CSF生物标志物在定义“淀粉样蛋白阳性”时被认为是可互换的。然而，Leuzy等人报告了多中心记忆诊所人群中这些指标之间的不一致性。这表明，在少数人中，这些指标可能是不可互换的，而是反映了不同但相互关联的过程。β淀粉样蛋白的PET和CSF生物标志物在定义“淀粉样蛋白阳性”时被认为是可互换的。然而，Leuzy等人报告了多中心记忆诊所人群中这些指标之间的不一致性。这表明，在少数人中，这些指标可能是不可互换的，而是反映了不同但相互关联的过程。本研究的目的是评估使用匹兹堡化合物B正电子发射断层扫描得出的脑淀粉样变性数据与（i）多实验室INNOTEST酶联免疫吸附测定得出的脑脊液淀粉样蛋白-β42浓度;（ii）使用Meso Scale Discovery酶联免疫吸附测定集中测量的脑脊液淀粉样蛋白-β42;和（iii）使用基于抗体非依赖性质谱的参考方法集中测量的脑脊液淀粉样蛋白-β42。此外，我们通过使用淀粉样蛋白-β42与淀粉样蛋白-β40的比率，检验了淀粉样蛋白生物标志物测量之间的不一致性可能是由于总淀粉样蛋白-β产生的个体间差异所致的假设。我们的研究人群包括来自阿尔茨海默病和帕金森病生物标志物倡议七个中心的243名受试者，包括认知正常的受试者和轻度认知障碍、阿尔茨海默病痴呆、额颞叶痴呆和血管性痴呆的患者。所有患者都有匹兹堡化合物B正电子发射断层扫描数据、脑脊液INNOTEST淀粉样蛋白-β42值和可用于再分析的脑脊液样本。使用Meso Scale Discovery电化学发光酶联免疫吸附测定技术和一种新型的抗体非依赖性质谱参考方法对脑脊液样本（淀粉样蛋白-β42和淀粉样蛋白-β40）进行再分析。使用Centiloid方法对匹兹堡化合物B标准化摄取值比值结果进行缩放。在轻度认知障碍和阿尔茨海默病受试者中，Meso Scale Discovery/质谱参考测量程序结果与匹兹堡化合物B之间的一致性较高，而在认知正常和非阿尔茨海默病组中观察到更多可变结果。当使用淀粉样蛋白β42/40时，匹兹堡化合物B分类与Meso Scale Discovery/质谱参考测量程序结果之间的一致性进一步提高。匹兹堡化合物B视觉评级和蜈蚣之间的协议是接近完成。尽管匹兹堡化合物B与集中分析的脑脊液之间的一致性提高，但少数受试者显示不一致的结果。虽然需要进一步研究，但我们的研究结果表明，淀粉样蛋白生物标志物的结果在某些个体中可能是不可互换的。
PET and CSF biomarkers of amyloid-β are considered interchangeable in defining ‘amyloid positivity’. However, Leuzy et al. report discordance between these measures in a multicentre memory clinic population. This suggests that in a minority of individuals these metrics may not be interchangeable, and may instead reflect distinct but interrelated processes. PET and CSF biomarkers of amyloid-β are considered interchangeable in defining ‘amyloid positivity’. However, Leuzy et al. report discordance between these measures in a multicentre memory clinic population. This suggests that in a minority of individuals these metrics may not be interchangeable, and may instead reflect distinct but interrelated processes. The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay derived cerebrospinal fluid concentrations of amyloid-β42; (ii) centrally measured cerebrospinal fluid amyloid-β42 using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-β42 centrally measured using an antibody-independent mass spectrometry-based reference method. Moreover, we examined the hypothesis that discordance between amyloid biomarker measurements may be due to interindividual differences in total amyloid-β production, by using the ratio of amyloid-β42 to amyloid-β40. Our study population consisted of 243 subjects from seven centres belonging to the Biomarkers for Alzheimer’s and Parkinson’s Disease Initiative, and included subjects with normal cognition and patients with mild cognitive impairment, Alzheimer’s disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-β42 values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-β42 and amyloid-β40) using Meso Scale Discovery electrochemiluminescence enzyme linked immunosorbent assay technology, and a novel, antibody-independent, mass spectrometry reference method. Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer’s disease, while more variable results were observed for cognitively normal and non-Alzheimer’s disease groups. Agreement between Pittsburgh compound B classification and Meso Scale Discovery/mass spectrometry reference measurement procedure findings was further improved when using amyloid-β42/40. Agreement between Pittsburgh compound B visual ratings and Centiloids was near complete. Despite improved agreement between Pittsburgh compound B and centrally analysed cerebrospinal fluid, a minority of subjects showed discordant findings. While future studies are needed, our results suggest that amyloid biomarker results may not be interchangeable in some individuals.